2019 Fiscal Year Final Research Report
A mechanism that switches the signaling specificity of Rho1 GTPase
| Project/Area Number |
16H04781
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Waseda University (2018-2019)
Gunma University (2016-2017) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
高稲 正勝 群馬大学, 未来先端研究機構, 助教 (20573215)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | RhoGTPase / PKC / PP2A / 酵母 |
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| Outline of Final Research Achievements |
Budding yeast Rho1 GTPase activates PKC-MAP kinase pathway in a stressful condition while it promote cell wall synthesis via PP2A-Cdc55 pathway in a growth condition. A key question in this study was to understand how Rho1 specifically select its targets (PKC and PP2A) in different growth conditions. We have shown that activity of both Rho1-PKC and Rho1-PP2A pathways are maintained by positive feedback mechanisms and that activity of PKC and PP2A are mutually antagonistic. Mutual antagonism between two Rho1 effectors may explain why only one pathway downstream of Rho1 is activated at a time.
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| Free Research Field |
細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
Rhoの過剰発現や異常な活性化は癌、糖尿病、神経疾患、発生異常等さまざまな疾患の原因となることが知られているが効率よくRhoの活性そのものを阻害する薬剤の開発はほとんど進んでいない。本研究ではRhoシグナル伝達系のアキレス腱として下流のエフェクターであるPKCとPP2A間の相互作用が重要であることを明らかにした。PKCやPP2Aという阻害剤開発が十分に進んでいる分子を標的とすることでRho関連疾患の制御や治療が可能であると期待される。
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